tbuckley/cabot-search huggingface dataset:
P10 Think zinc: nutritional deficiency in a breastfed infant associated with antenatal proton-pump inhibitor exposure
Authors: Emma Porter, Oonagh Molloy, Michelle Murphy, Cathal O’Connor
Journal: British Journal of Dermatology (2023)

Abstract A 5-month-old infant presented with a 3-month history of a dramatic periorofacial and acral dermatitis associated with recurrent infections, increasing lethargy and poor feeding. He was born at full term, breastfed exclusively, and had no family history of skin disease. Serum alkaline phosphatase was 41 (range 82–383) and zinc levels were undetectably low (&amp;lt; 3 mg mol–1; normal 10–25). Maternal breastmilk zinc levels were low (3.15, control mean 12.7), and maternal serum zinc was normal. A rapid improvement was noted within days of zinc sulfate supplementation. Zinc supplementation was stopped after 3 months, with normal follow-up zinc levels. The mother had taken omeprazole from 30 weeks’ gestation to birth. In her previous pregnancy there was no proton-pump inhibitor (PPI) ingestion, and no manifestation of zinc deficiency in the older sibling, who had also been breastfed exclusively. Maternal genetic testing for defects in SLC30A2, a zinc transporter in mammary tissue, was negative. Acrodermatitis enteropathica involves recessive mutations in the SLC39A4 gene, and secondary transient infantile zinc deficiency can be due to prematurity, low zinc intake, or malabsorptive processes such as cystic fibrosis. It is rare in breastfed infants due to enhanced bioavailability of zinc. PPIs can decrease serum zinc due to intestinal chelation, although little is known regarding their effect on transplacental or transmammary zinc transmission. To our knowledge this is the first report of zinc deficiency in a breastfed infant associated with maternal PPI use, potentially due to diminished transmammary and/or transplacental zinc transmission.
P12 #corticophobia: a review of misinformation related to topical steroids
Authors: Paula Finnegan, Michelle Murphy, Cathal O’Connor
Journal: British Journal of Dermatology (2023)

Abstract Misinformation in healthcare is now at crisis level worldwide, with the internet as the primary source of prevarication. Topical corticosteroids (TCS) are a safe and effective treatment used in multiple conditions in paediatric dermatology. Nonadherence to prescribed TCS can be due to phobia secondary to misinformation, and poor compliance is a common obstacle to disease control. TCS phobia is a complex, multifaceted phenomenon that exploits children with skin disease and obstructs their path to successful treatment. This study aims to examine the content of TCS-related misinformation available online. A formal review of PubMed was performed in June 2022, using the terms ‘topical corticosteroids’ AND ‘misinformation’ OR ‘disinformation’ OR ‘conspiracy theory’, along with an informal Google search using combinations of these terms, and further targeted searches on social media applications including Facebook, Twitter, Instagram and TikTok. The main fears expressed by children and parents regarding TCS included potential adverse effects (skin thinning, stunted growth/development). ‘Topical steroid withdrawal’, ‘red skin syndrome’ or ‘TCS addiction’ is a particularly prevalent myth currently being propagated on social media, with most content suggesting that eczema is due to a ‘leaky gut’ and not skin inflammation. Numerous websites promoting misinformation were frequently endorsed by companies advertising ‘natural’ products as treatment alternatives, including ‘herbal’ remedies which can contain significant quantities of corticosteroids or other potent ingredients. The paediatric dermatology community should be vigilant of the type of TCS-related misinformation online, and actively attempt to counteract it with evidence-based advice.
O08 Mesenchymal stromal cells infusions in children with recessive dystrophic epidermolysis bullosa (MissionEB): a randomized controlled trial
Authors: Maria L Bageta, Pablo Lopez Balboa, Rachel Glover, Cindy Cooper, Diana E Papaioannou, Steven Julious, Munya Dimairo, Katie Biggs, Gabriela Petrof, Anna E Martinez
Journal: British Journal of Dermatology (2023)

Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is one of the most severe forms of epidermolysis bullosa caused by loss-of-function mutations in the type VII collagen gene (COL7A1) leading to extensive skin and mucosal fragility and systemic complications. No active treatment is currently available. This study assesses whether repeated infusions of allogeneic umbilical cord-derived mesenchymal stromal cells are safe and can benefit children with RDEB. This is a double-blinded, randomized (1 : 1), placebo-controlled crossover trial with an internal dose de-escalation trial for safety and a further 12-month open-label study following review of the data. Around 36 participants with RDEB who are older than 6 months and younger than 16 years are being recruited at Great Ormond Street Hospital and Birmingham Children's Hospital. Participants will receive two intravenous infusions (days 0 and 14), at a dose of 2–3 × 106 cells kg–1 that could be adjusted to 1–1.5 × 106 cells kg–1 based on observed toxicities. Outcomes assessed at 3 and 6 months from day 0 in each crossover period include changes in EBDASI, iscorEB, pain, itch and quality of life scores. This is the largest cell-therapy study in children with RDEB. Previous nonrandomized trials have suggested that intravenous mesenchymal stromal cells are safe in children with RDEB and indicated early evidence of benefit. There was a need for a robust controlled study to validate these findings. The study is funded by the National Research Collaboration Programme (NIHR127963), an NHS England and NHS Improvement and National Institute for Health Research partnership, and Cure EB. ISRCTN registry (ISRCTN14409785).
P16 Linear bullous aplasia cutis congenita of the scalp: an unusual presentation of a rare condition
Authors: Karina Forde, Zainab Zawafta, Nigel Burrows
Journal: British Journal of Dermatology (2023)

Abstract Aplasia cutis congenita (ACC) is a heterogenous group of congenital disorders characterized by focal or widespread absence of skin. Bullous ACC is a rare variant that presents with well-circumscribed oval lesions resembling bullae or vesicles covered with a thin membrane. There have been 20 previously reported cases of bullous ACC. We present a female neonate referred to dermatology at day 2 of life following an IVF-assisted pregnancy and delivery by elective caesarean section for breech presentation. There was no antenatal history of infection, trauma or drugs, and no relevant family history. Clinical examination of the parietal scalp revealed five well-demarcated bullae in a linear distribution along Blaschko lines. The hair collar and ‘golf club set’ signs were absent. Skin swabs for microbiology and viral studies were negative. Ultrasonography showed no associated osseous defect. Clinical examination was otherwise normal. A diagnosis of multibullous ACC was made, and a conservative approach adopted. Clinical follow up at 2 years found resorption of one bulla with flattening of the remainder. Neurodevelopment was normal. On review of the literature, 10/20 (50%) cases of bullous ACC presented with multiple bullae. The hair collar sign was positive in 50%, strengthening theories that bullous ACC may represent a ‘forme fruste’ of a neural tube defect. Four other cases reported distribution along Blashko lines, suggesting possible underlying cutaneous mosaicism. The majority (90%) had no associated cutaneous or extracutaneous findings. Clinical outcomes were good with spontaneous resorption of bullae, suggesting conservative management is appropriate in most cases.
P31 Eyeing up: dupilumab-associated ocular surface disease in children with eczema in a tertiary paediatric hospital in London
Authors: Anjali Rampersad, Karolina Gholam, Lea Solman, Natalia Cartledge, Sri Gore, Gabriela Petrof
Journal: British Journal of Dermatology (2023)

Abstract Dupilumab blocks interleukin (IL)-4 and IL-13 and has demonstrated significant clinical benefit in eczema. Dupilumab-associated ocular-surface disease (DAOSD) has been described in adults but literature on the paediatric population is scarce. We conducted a retrospective review of electronic patient records of patients receiving dupilumab for eczema from April 2019 to July 2022. Outcome measures included incidence of DAOSD, patient/drug-related risk factors, ocular signs and symptoms, time to develop DAOSD, severity and treatments. Forty-six patients (median age 12 years, range 9–14) were identified; of these 12 (26%) developed DAOSD. Only one patient (8.3%) had pre-existing eye disease. The median time to DAOSD development was 3 (1–9) months. All patients were referred to ophthalmology, nine have been reviewed and three are awaiting appointments. All but one was symptomatic with ocular irritation (92%). In the nine patients reviewed by ophthalmology, ocular signs included bilateral bulbar conjunctival injection (n = 9, 100%), follicles (limbal or forniceal, n = 4, 44%), diffuse tarsal–conjunctival thickening (n = 3, 33%), cicatrization (n = 2, 22%). Four patients (44%) had moderate eye findings with peripheral corneal opacification; the symptoms were not always proportionate to the signs. The remaining five patients had mild ocular findings. Topical treatment for DAOSD included protopic to eyelid (n = 1), ciclosporin (n = 2), steroid (n = 4), lubrication (n = 5) and chloramphenicol (n = 2). No patients stopped treatment because of DAOSD. DAOSD in this cohort was higher than that reported in RCTs with similar timeframe to DAOSD development. Almost half of our patient cohort had moderate DAOSD but were only mildly symptomatic. No DAOSD predictive factors were identified.
O03 Langerhans cell histiocytosis: case series of presentations to dermatology in the <i>BRAF</i> era
Authors: Conor Coyle, Louise Bovijn, Esther Blanco, Tess McPherson
Journal: British Journal of Dermatology (2023)

Abstract Langerhans cell histiocytosis (LCH) is a rare disease driven by MAPK pathway mutations. This condition is on a spectrum, from single-system to life-threatening multisystem disease. Identification of the BRAF mutation is leading to improved understanding and targeted therapies. However, there is limited information on genetic status, phenotype and dermatological features. Fourteen patients were seen in the Paediatric Dermatology department in period 2015–2022: 11 males and 3 females; 9 patients had multisystem LCH; 8 patients had cutaneous manifestations of LCH; and 4 had limited cutaneous LCH. Six patients were diagnosed in the department and typically had multiple incorrect diagnoses and treatments prior to review. Clinical features varied from widespread skin involvement, scalp/groin intertrigo, flexural ulcerations and telangiectatic papules. Eight had LCH diagnosed in other tissues by oncology and referral advice on cutaneous symptoms were sought. Most patients have required input from dermatology throughout treatment. Biopsies were taken when unclear diagnosis and/or pathology would influence treatment. Several consultations revealed benign pathologies including keratosis pilaris and dermatitis requiring topical treatment advice only. All five patients with BRAF v600 mutation had multisystem disease including diabetes insipidus, adrenal insufficiency, gut and bone lesions. Two patients with severe LCH and BRAF mutations are being treated successfully with dabrafenib. Our series demonstrates the important role of dermatology in the diagnosis and management of LCH. This series confirms clinical heterogeneity and an association of BRAF V600E mutation with multiorgan disease. Ongoing work should expand our knowledge of the relationship of genetic alterations with clinical phenotypes and comorbidities.
O05 Management of acute desloughing of the oesophageal lining in patients with dystrophic epidermolysis bullosa: a case series of six paediatric patients
Authors: Maria Bageta, Pablo Lopez Balboa, Natalie Yerlett, Anna Rybak, Gabriela Petrof, Anna Martinez
Journal: British Journal of Dermatology (2023)

Abstract Dystrophic epidermolysis bullosa (DEB) is a subtype of inherited skin disorders characterized by skin and mucosal fragility due to collagen VII (COL7A1) gene mutations. Desloughing of the lining of the oesophagus has not been reported before. We retrospectively reviewed the hospital electronic patient records between 2008 and 2021 with regard to acute treatment and long-term management. Six patients with recessive DEB (RDEB) severe (n = 4), RDEB intermediate (n = 1) and dominant DEB (DDEB) were identified. The mean age at the time of the episode was 29.6 months. Most of the patients (n = 5) suffered from severe gastro-oesophageal reflux at the time of onset. Clinically, they presented with a coughing episode (n = 6), haematemesis (n = 6), vomiting (n = 6) and choking (n = 3) with a piece of mucosae coughed up. Four patients recovered with medical management including immediate hospitalization, no oral intake (nil by mouth, NBM), pain relief and optimization of the dose of proton-pump inhibitors. Due to severe persistent dysphagia, two patients required gastrostomy insertions for feeding; one also required a Nissen's fundoplication due to severe reflux. One patient had an aspiration pneumonia. Desloughing of varying lengths of segments of the oesophagus is an emergency. The lining coughed up needs to be cut at the mouth not pulled and the emergency services called immediately. On arrival, an urgent assessment and chest X-ray should be performed to rule out any signs of perforation. The patient should be kept NBM with intravenous fluids and pain relief. Expert multidisciplinary care is needed to manage this rare but extremely serious condition.
Growth-dependent Gene Expression Variation Influences the Strength of Codon Usage Biases
Authors: Mackenzie M Johnson, Adam J Hockenberry, Matthew J McGuffie, Luiz Carlos Vieira, Claus O Wilke
Journal: Molecular Biology and Evolution (2023)

The most highly expressed genes in microbial genomes tend to use a limited set of synonymous codons, often referred to as "preferred codons." The existence of preferred codons is commonly attributed to selection pressures on various aspects of protein translation including accuracy and/or speed. However, gene expression is condition-dependent and even within single-celled organisms transcript and protein abundances can vary depending on a variety of environmental and other factors. Here, we show that growth rate-dependent expression variation is an important constraint that significantly influences the evolution of gene sequences. Using large-scale transcriptomic and proteomic data sets in Escherichia coli and Saccharomyces cerevisiae, we confirm that codon usage biases are strongly associated with gene expression but highlight that this relationship is most pronounced when gene expression measurements are taken during rapid growth conditions. Specifically, genes whose relative expression increases during periods of rapid growth have stronger codon usage biases than comparably expressed genes whose expression decreases during rapid growth conditions. These findings highlight that gene expression measured in any particular condition tells only part of the story regarding the forces shaping the evolution of microbial gene sequences. More generally, our results imply that microbial physiology during rapid growth is critical for explaining long-term translational constraints.
P02 A case of congenital panhypopituitarism unmasked by PHACE screening
Authors: Paula Finnegan, Nicholas Clarke, John Twomey, Orla Neylon, Muriel Sadlier
Journal: British Journal of Dermatology (2023)

Abstract PHACE syndrome is a rare neurocutaneous disorder referring to the association of segmental infantile haemangiomas (IH) with congenital brain, arterial, cardiac, eye and mid-line anomalies. Endocrinopathies have infrequently been reported with PHACE syndrome. We present a case of congenital panhypopituitarism detected during PHACE workup. A 7-week-old girl presented with a large 4 × 4 cm superficial partially segmental IH on the mid-neck and three small superficial IHs on the scalp and trunk. She was born at term following an uncomplicated pregnancy. She had a 10-day NICU admission for neonatal hypoglycaemia and hypotonia which had fully resolved. Brain MRI showed an ectopic pituitary gland and an absent pituitary stalk. No other vascular, cardiac or intracranial abnormalities were identified. Dynamic pituitary testing demonstrated severe cortisol deficiency (&amp;lt; 3), central hypothyroidism (TSH 1.82, free T4 9.2) and undetectable gonadotrophins (LH &amp;lt; 1.0, FSH &amp;lt; 1.0), consistent with congenital panhypopituitarism. She was commenced on hormone replacement therapy by endocrinology. A dramatic behavioural difference was noted by her parents within days of starting treatment with increased alertness and less daytime somnolence. Of note there had been no medical or developmental concerns prior to her screening. Her heel prick test had not detected hypothyroidism. She was commenced on propranolol 2 mg kg–1 daily for her IH with excellent response and tolerability. Congenital or acquired endocrinopathy can occur in PHACE syndrome both in the presence and absence of pituitary defects. It is important to be aware of endocrine manifestations in these patients.
P11 Pooling the evidence: a review of swimming and atopic dermatitis
Authors: Cathal O’Connor, Siobhan McCarthy, Michelle Murphy
Journal: British Journal of Dermatology (2023)

Abstract Swimming is an excellent form of aerobic exercise and is an essential life skill. Many children with atopic dermatitis (AD) are advised not to swim because of concerns about negative impacts on their skin disease, and some children with AD do not swim because they are self-conscious about the appearance of their skin. We aimed to review the available literature on swimming and AD and scientifically analyse the potential impact of all components of swimming in AD – water, skin barrier, swimming gear and exercise. Studies examined the impact of swimming on the skin barrier and relative contraindications to swimming. Constituents of water that may affect AD include hardness, pH, temperature, antiseptics and other chemicals. Potential interventions to reduce damage included emollient application, special swim gear, and showering post-submersion. The benefits of swimming as a form of exercise in AD included reduced sweating, cardiorespiratory fitness and maintenance of healthy weight. Drawbacks of swimming as a form of exercise in AD included the limited benefit on bone mineral density. Future research should examine the impact of swimming on flares of AD using noninvasive biomarkers as well as clinical severity assessment, and assess the role for different types of emollient as an intervention for optimal eczema control. Based on the review we provide new guidance on how to advise parents and children with AD regarding general measures, swim wear, and pool-side interventions to minimize any deleterious effect on skincare, and maximize opportunities to swim.
P22 Life-threatening bleeding is a serious potential complication of ulcerated congenital haemangiomas: three case reports
Authors: Hadi Alenezi, Lea Solman
Journal: British Journal of Dermatology (2023)

Abstract Congenital haemangiomas (CH) are rare vascular tumours that can be complicated by high-output heart failure (HOHF), transient thrombocytopaenia and ulceration. We present three patients who had life-threatening bleeding from the ulcerated CH, which was fatal for one of the patients. The first patient was born with a large CH of his left thigh, causing thrombocytopaenia and HOHF, requiring ventilation. He was discharged home after 3 weeks, but subsequently developed an ulceration and had a profuse bleeding following a dressing change at home. He required admission to PICU and ventilation support. The second patient was born with a large segmental CH of his right scalp with two ulcerated areas, without HOHF or thrombocytopaenia. He developed a massive bleeding from the ulcerated area at 6 weeks of age, was admitted to PICU with cardiac arrest, but died a few hours later due to multiorgan failure. The third patient was born at 29 weeks’ gestation with a large CH of her right thigh which was ulcerated. She had a profuse arterial bleeding after the dressing was removed in the hospital, requiring emergency surgery and admission to PICU. Although it is a rare complication, neonates/infants with ulcerated CH are at risk for severe, life-threatening arterial bleeding. If an ulceration is present, it needs to be protected with a suitable dressing, until it heals completely. Parents need to be educated on appropriate dressing changing technique, have the support of local tissue viability nurses and learn basic CPR techniques should arterial bleeding occur and necessitate CPR.
O10 Cohort study of paradoxical psoriasis in an adolescent population receiving anti-tumour necrosis factor-α for inflammatory bowel disease in a large teaching hospital with specialist dermatology and paediatric gastroenterology services
Authors: Narin Shareef, Josephina Price, Leila Ferguson, Alya Abdul-Wahab
Journal: British Journal of Dermatology (2023)

Abstract Paradoxical psoriasis is well recognized in adults receiving anti-tumour necrosis factor-(TNF)-α therapy for inflammatory bowel disease (IBD) [Bucalo A, Rega F, Zangrilli A et al. Paradoxical psoriasis induced by anti-TNFα treatment: evaluation of disease-specific clinical genetic markers. Int J Mol Sci 2020; 21: 7873. https://doi.org/10.3390/ijms21217873]. Biologics are increasingly being initiated earlier in the treatment ladder for IBD in the paediatric population, who are also vulnerable to paradoxical psoriasis. This observational study aimed to describe the clinical features and management in this group, as there are limited data on how paradoxical psoriasis differs in children. Eight patients with paradoxical psoriasis were referred between 2019 and 2022: five females and three males; age range 12–19 years (mean 15.4 years). They all had Crohn disease and were receiving infliximab (7/8 patients) or adalimumab (1/8). The onset of symptoms following anti-TNF-α initiation was 3 months to 3 years (mean 12.75 months). Involvement included scalp (7), flexural areas (3), trunk (4) limb (3) and face (1). In adults, palmoplantar and pustular forms were commonly reported whereas our cohort demonstrated eczematous forms requiring antibacterial agents, rarely seen in adults. Management included switching from infliximab to ustekinumab in three patients; and the addition of methotrexate (two). Topical treatments alone were sufficient in three patients. There were florid presentations in our cohort and the scalp was predominantly affected (7/8). Five of eight patients required a switch of their anti-TNF-α therapy or an additional systemic treatment. It is crucial for physicians to be aware of this phenomenon and work collaboratively to recognize this early to optimize patients’ symptoms and quality of life [Bucalo et al.].